Chris Gale

Preterm Birth and the Metabolic Syndrome in Adult Life: A Systematic Review and Meta-analysis

BACKGROUND: Preterm birth is associated with features of the metabolic syndrome in later life. We performed a systematic review and meta-analysis of studies reporting markers of the metabolic syndrome in adults born preterm. METHODS: Reports of metabolic syndrome–associated features in adults (≥18 years of age) born at <37-week gestational age and at term (37- to 42-week gestational age) were included. Outcomes assessed were BMI, waist-hip ratio, percentage fat mass, systolic (SBP) and diastolic (DBP) blood pressure, 24-hour ambulatory SBP and DBP, flow-mediated dilatation, intima-media thickness, and fasting glucose, insulin, and lipid profiles. RESULTS: Twenty-seven studies, comprising a combined total of 17 030 preterm and 295 261 term-born adults, were included. In adults, preterm birth was associated with significantly higher SBP (mean difference, 4.2 mm Hg; 95% confidence interval [CI], 2.8 to 5.7; P < .001), DBP (mean difference, 2.6 mm Hg; 95% CI, 1.2 to 4.0; P < .001), 24-hour ambulatory SBP (mean difference, 3.1 mm Hg; 95% CI, 0.3 to 6.0; P = .03), and low-density lipoprotein (mean difference, 0.14 mmol/L; 95% CI, 0.05 to 0.21; P = .01). The preterm–term differences for women was greater than the preterm–term difference in men by 2.9 mm Hg for SBP (95% CI [1.1 to 4.6], P = .004) and 1.6 mm Hg for DBP (95% CI [0.3 to 2.9], P = .02). CONCLUSIONS: For the majority of outcome measures associated with the metabolic syndrome, we found no difference between preterm and term-born adults. Increased plasma low-density lipoprotein in young adults born preterm may represent a greater risk for atherosclerosis and cardiovascular disease in later life. Preterm birth is associated with higher blood pressure in adult life, with women appearing to be at greater risk than men.

Effect of breastfeeding compared with formula feeding on infant body composition: a systematic review and meta-analysis

BACKGROUND Early-life nutrition may influence later body composition. The effect of breastfeeding and formula feeding on infant body composition is uncertain. OBJECTIVE We conducted a systematic review and meta-analysis of studies that examined body composition in healthy, term infants in relation to breastfeeding or formula feeding. DESIGN PubMed was searched for human studies that reported the outcomes fat-free mass, fat mass, or the percentage of fat mass in breastfed and formula-fed infants. Bibliographies were hand searched, and authors were contacted for additional data. The quality of studies was assessed. Differences in outcomes between feeding groups were compared at prespecified ages by using fixed-effects analyses except when heterogeneity indicated the use of random-effects analyses. RESULTS We identified 15 studies for inclusion in the systematic review and 11 studies for inclusion in the meta-analysis. In formula-fed infants, fat-free mass was higher at 3-4 mo [mean difference (95% CI): 0.13 kg (0.03, 0.23 kg)], 8-9 mo [0.29 kg (0.09, 0.49 kg)], and 12 mo [0.30 kg (0.13, 0.48 kg)], and fat mass was lower at 3-4 mo [-0.09 kg (-0.18, -0.01 kg)] and 6 mo [-0.18 kg (-0.34, -0.01 kg)] than in breastfed infants. Conversely, at 12 mo, fat mass was higher in formula-fed infants [0.29 kg (-0.03, 0.61 kg)] than in breastfed infants. CONCLUSION Compared with breastfeeding, formula feeding is associated with altered body composition in infancy.

The diabetic pregnancy and offspring BMI in childhood: a systematic review and meta-analysis.

Aims/hypothesisOffspring of mothers with diabetes are at increased risk of metabolic disorders in later life. Increased offspring BMI is a plausible mediator. We performed a systematic review and meta-analysis of studies examining offspring BMI z score in childhood in relation to maternal diabetes.MethodsPapers reporting BMI z scores for offspring of diabetic (all types, and pre- and during-pregnancy onset) and non-diabetic mothers were included. Citations were identified in PubMed; bibliographies of relevant articles were hand-searched and authors contacted for additional data where necessary. We compared offspring BMI z score with and without adjustment for maternal pre-pregnancy BMI. We performed fixed effect meta-analysis except where significant heterogeneity called for use of a random effects analysis.ResultsData were available from nine studies. In the diabetic group unadjusted mean offspring BMI z score was 0.28 higher (all diabetic mothers vs controls (95% CI 0.09, 0.47; p = 0.004; nine studies; offspring of diabetic mothers n = 927, controls n = 26,384) and with adjustment for maternal pre-pregnancy BMI, 0.07 higher (95% CI −0.15, 0.28; p = 0.54; three studies; offspring of diabetic mothers n = 244, controls n = 11,206). There was no evidence of a difference in offspring BMI z score in relation to type of diabetes (gestational vs type 1, p = 0.95).Conclusions/interpretationMaternal diabetes is associated with increased offspring BMI z score, although this is no longer apparent after adjustment for maternal pre-pregnancy BMI in the limited number of studies in which this is reported. Causal mediators of the effect of maternal diabetes on offspring outcomes remain to be established; we recommend that future research includes adjustment for maternal pre-pregnancy BMI.

Mode of Delivery and Offspring Body Mass Index, Overweight and Obesity in Adult Life: A Systematic Review and Meta-Analysis

Background It has been suggested that mode of delivery, a potentially powerful influence upon long-term health, may affect later life body mass index (BMI). We conducted a systematic review and meta-analysis of the effect of Caesarean section (CS) and vaginal delivery (VD) on offspring BMI, overweight (BMI>25) and obesity (BMI>30) in adulthood. Secondary outcomes were subgroup analyses by gender and type of CS (in-labour/emergency, pre-labour/elective). Methods Using a predefined search strategy, Pubmed, Google Scholar and Web of Science were searched for any article published before 31st March 2012, along with references of any studies deemed relevant. Studies were selected if they reported birth characteristics and long-term offspring follow-up into adulthood. Aggregate data from relevant studies were extracted onto a pre-piloted data table. A random-effects meta-analysis was carried out in RevMan5. Results are illustrated using forest plots and funnel plots, and presented as mean differences or odds ratios (OR) and 95% confidence intervals. Results Thirty-five studies were identified through the search, and 15 studies with a combined population of 163,753 were suitable for inclusion in the meta-analysis. Comparing all CS to VD in pooled-gender unadjusted analyses, mean BMI difference was 0·44 kg·m-2 (0·17, 0·72; p = 0·002), OR for incidence of overweight was 1·26 (1·16, 1·38; p<0·00001) and OR for incidence of obesity was 1·22 (1·05, 1·42; p = 0·01). Heterogeneity was low in all primary analyses. Similar results were found in gender-specific subgroup analyses. Subgroup analyses comparing type of CS to VD showed no significant impact on any outcome. Conclusions There is a strong association between CS and increased offspring BMI, overweight and obesity in adulthood. Given the rising CS rate worldwide there is a need to determine whether this is causal, or reflective of confounding influences. Systematic review registration An a priori protocol was registered on PROSPERO (registration number: CRD42011001851)

Changing Characteristics and Mode of Death Associated With Chronic Heart Failure Caused by Left Ventricular Systolic Dysfunction A Study Across Therapeutic Eras

Background—Therapies for patients with chronic heart failure caused by left ventricular systolic dysfunction have advanced substantially over recent decades. The cumulative effect of these therapies on mortality, mode of death, symptoms, and clinical characteristics has yet to be defined. Methods and Results—This study was a comparison of 2 prospective cohort studies of outpatients with chronic heart failure caused by left ventricular systolic dysfunction performed between 1993 and 1995 (historic cohort: n=281) and 2006 and 2009 (contemporary cohort: n=357). In the historic cohort, 83% were prescribed angiotensin-converting enzyme inhibitors and 8.5% were prescribed &bgr;-adrenoceptor antagonists, compared with 89% and 80%, respectively, in the contemporary cohort. Mortality rates over the first year of follow-up declined from 12.5% to 7.8% between eras (P=0.04), and sudden death contributed less to contemporary mortality (33.6% versus 12.7%; P<0.001). New York Heart Association class declined between eras (P<0.001). QTc dispersion across the chest leads declined from 85 ms (SD, 2) to 34 ms (SD, 1) and left ventricular end-diastolic dimensions declined from 65 mm (SD, 0.6) to 59 mm (SD, 0.5) (both P<0.001). Conclusions—Survival has significantly improved in patients with chronic heart failure caused by left ventricular systolic dysfunction over the past 15 years; furthermore, sudden death makes a much smaller contribution to mortality, and noncardiac mortality is a correspondingly greater contribution. This has been accompanied by an improvement in symptoms and some markers of adverse electric and structural left ventricular remodeling.

Effect of maternal body mass index on hormones in breast milk: a systematic review.

Background Maternal Body Mass Index (BMI) is positively associated with infant obesity risk. Breast milk contains a number of hormones that may influence infant metabolism during the neonatal period; these may have additional downstream effects on infant appetite regulatory pathways, thereby influencing propensity towards obesity in later life. Objective To conduct a systematic review of studies examining the association between maternal BMI and the concentration of appetite-regulating hormones in breast milk. Method Pubmed was searched for studies reporting the association between maternal BMI and leptin, adiponectin, insulin, ghrelin, resistin, obestatin, Peptide YY and Glucagon-Like Peptide 1 in breast milk. Results Twenty six studies were identified and included in the systematic review. There was a high degree of variability between studies with regard to collection, preparation and analysis of breast milk samples. Eleven of fifteen studies reporting breast milk leptin found a positive association between maternal BMI and milk leptin concentration. Two of nine studies investigating adiponectin found an association between maternal BMI and breast milk adiponectin concentration; however significance was lost in one study following adjustment for time post-partum. No association was seen between maternal BMI and milk adiponectin in the other seven studies identified. Evidence for an association between other appetite regulating hormones and maternal BMI was either inconclusive, or lacking. Conclusions A positive association between maternal BMI and breast milk leptin concentration is consistently found in most studies, despite variable methodology. Evidence for such an association with breast milk adiponectin concentration, however, is lacking with additional research needed for other hormones including insulin, ghrelin, resistin, obestatin, peptide YY and glucagon-like peptide-1. As most current studies have been conducted with small sample sizes, future studies should ensure adequate sample sizes and standardized methodology.

Changing Characteristics and Mode of Death Associated With Chronic Heart Failure Caused by Left Ventricular Systolic DysfunctionClinical Perspective

Background—Therapies for patients with chronic heart failure caused by left ventricular systolic dysfunction have advanced substantially over recent decades. The cumulative effect of these therapies on mortality, mode of death, symptoms, and clinical characteristics has yet to be defined. Methods and Results—This study was a comparison of 2 prospective cohort studies of outpatients with chronic heart failure caused by left ventricular systolic dysfunction performed between 1993 and 1995 (historic cohort: n=281) and 2006 and 2009 (contemporary cohort: n=357). In the historic cohort, 83% were prescribed angiotensin-converting enzyme inhibitors and 8.5% were prescribed &bgr;-adrenoceptor antagonists, compared with 89% and 80%, respectively, in the contemporary cohort. Mortality rates over the first year of follow-up declined from 12.5% to 7.8% between eras (P=0.04), and sudden death contributed less to contemporary mortality (33.6% versus 12.7%; P<0.001). New York Heart Association class declined between eras (P<0.001). QTc dispersion across the chest leads declined from 85 ms (SD, 2) to 34 ms (SD, 1) and left ventricular end-diastolic dimensions declined from 65 mm (SD, 0.6) to 59 mm (SD, 0.5) (both P<0.001). Conclusions—Survival has significantly improved in patients with chronic heart failure caused by left ventricular systolic dysfunction over the past 15 years; furthermore, sudden death makes a much smaller contribution to mortality, and noncardiac mortality is a correspondingly greater contribution. This has been accompanied by an improvement in symptoms and some markers of adverse electric and structural left ventricular remodeling.

Core outcome sets in women's and newborn health: a systematic review

Variation in outcome collection and reporting is a serious hindrance to progress in our specialty; therefore, over 80 journals have come together to support the development, dissemination, and implementation of core outcome sets.

Persistent geographical disparities in the use of primary percutaneous coronary intervention in 120 European regions: exploring the variation.

AIMS Large inequalities in the use of primary percutaneous interventions (PPCI) for ST-elevation myocardial infarction (STEMI) are evident. In order to understand how we can help to implement best practice for STEMI patients, we investigated the variation in PPCI utilisation in 120 regions in 10 EU countries and the association with economic, organisational and demographic characteristics. METHODS AND RESULTS We performed an ecological study using mixed effects regression models in the following 10 countries: Austria, Belgium, Denmark, England and Wales, Germany, Italy, Portugal, Spain, Sweden, and Northern Ireland. The main finding was the annual number of PPCI per million inhabitants from 2003 through 2008. Overall, the annual increase in PPCI utilisation was 1.15 (95% CI: 1.12, 1.19) per million per year. Regional-level rates varied from 0.74 (95% CI: 0.42, 1.30) to 1.90 (95 % CI: 1.01, 3.55) per million per year. At a regional level, significant positive associations with PPCI utilisation were the number of physicians per 100,000 inhabitants; the number of nurses and midwives per 100,000 inhabitants; and the proportion of the regions population aged 50 to <70 years. At a country level, significant positive associations with utilisation were the year of STEMI treatment, population density per km2; number of general hospital beds per 100,000 inhabitants; and the number of physicians per 100,000 inhabitants. CONCLUSIONS Between 2003 and 2008, PPCI utilisation increased significantly in the ten European countries studied, but there was a great variation within country regions. Regional variation in PPCI rates were associated with both demographic and supply factors, revealing substantial opportunities to improve PPCI utilisation across Europe at national and regional levels.

Avoiding sedation in research MRI and spectroscopy in infants: our approach, success rate and prevalence of incidental findings

Performing magnetic resonance investigations in a paediatric population can be difficult; image acquisition is commonly complicated by movement artefact and non-compliance. Sedation is widely used for clinically indicated investigations, but there is controversy when used for research imaging. Over a 10-year period we have performed whole body MRI on over 450 infants and hepatic magnetic resonance spectroscopy on over 270 infants. These investigations have been accomplished without the use of sedation in infants up to 3 months of age. Our overall success rate in achieving good quality images free of movement artefact is 94%. The prevalence of incidental findings on whole body (excluding brain) MRI in our cohort was 0.8%. We conclude that the use of sedation for research MRI in this group is not necessary. Our approach to MRI in infancy is also described.